mTORC2 regulates PGE2-mediated endothelial cell survival and migration.

Prostaglandin E(2) (PGE(2)) promotes angiogenesis by in part inducing endothelial cell survival and migration. The present study examined the role of mTOR and its two complexes, mTORC1 and mTORC2, in PGE(2)-mediated endothelial cell responses. We used small interfering RNA (siRNA) to raptor or rictor to block mTORC1 or mTORC2, respectively. We observed that down-regulation of mTORC2 but not mTORC1 reduced baseline and PGE(2)-induced endothelial cell survival and migration. At the molecular level, we found that knockdown of mTORC2 inhibited PGE(2)-mediated Rac and Akt activation two important signaling intermediaries in endothelial cell migration and survival, respectively. In addition, inhibition of mTORC2 by prolonged exposure of endothelial cells to rapamycin also prevented PGE(2)-mediated endothelial cell survival and migration confirming the results obtained with the siRNA approach. Taken together these results show that mTORC2 but not mTORC1 is an important signaling intermediary in PGE(2)-mediated endothelial cell responses.

Differential migration of in vivo primed B and T lymphocytes to lymphoid and non-lymphoid organs.

Our study describes tissue-specific migration of T and B cells during a localized anti-viral immune response. After mouse mammary tumor virus (MMTV) injection, B lymphocytes of the draining lymph node become infected and present a retroviral superantigen to CD4(+) T lymphocytes. Infected B cells receive superantigen-mediated help in a fashion comparable to classical immune responses. To investigate the fate of T and B lymphocytes that had interacted via cognate help in the same peripheral lymph node microenvironment we adoptively transferred them into naive recipients. Here we show that MMTV-infected B cells and superantigen-stimulated T cells were programmed to migrate to distinct sites of the body. Plasmablasts but not T cells migrated to the mammary gland and activated alpha4beta1 integrins were found to have a crucial role in the migration to the mammary gland. In contrast, T cells had a much higher affinity for secondary lymphoid organs and large intestine. This demonstrates that upon antigen-driven B and T lymphocyte interaction in the local draining lymph node a subset-specific homing program for B and T lymphocytes is induced.

Helicase-defective RuvB(D113E) promotes RuvAB-mediated branch migration in vitro.

In Escherichia coli, the RuvA and RuvB proteins interact at Holliday junctions to promote branch migration leading to the formation of heteroduplex DNA. RuvA provides junction-binding specificity and RuvB drives ATP-dependent branch migration. Since RuvB contains sequence motifs characteristic of a DNA helicase and RuvAB exhibit helicase activity in vitro, we have analysed the role of DNA unwinding in relation to branch migration. A mutant RuvB protein, RuvB(D113E), mutated in helicase motif II (the DExx box), has been purified to homogeneity. The mutant protein forms hexameric rings on DNA similar to those formed by wild-type protein and promotes branch migration in the presence of RuvA. However, RuvB(D113E) exhibits reduced ATPase activity and is severely compromised in its DNA helicase activity. Models for RuvAB-mediated branch migration that invoke only limited DNA unwinding activity are proposed.

The Fanconi anemia protein FANCM can promote branch migration of Holliday junctions and replication forks.

Fanconi anemia (FA) is a genetically heterogeneous cancer-prone disorder associated with chromosomal instability and cellular hypersensitivity to DNA crosslinking agents. The FA pathway is suspected to play a crucial role in the cellular response to DNA replication stress. At a molecular level, however, the function of most of the FA proteins is unknown. FANCM displays DNA-dependent ATPase activity and promotes the dissociation of DNA triplexes, but the physiological significance of this activity remains elusive. Here we show that purified FANCM binds to Holliday junctions and replication forks with high specificity and promotes migration of their junction point in an ATPase-dependent manner. Furthermore, we provide evidence that FANCM can dissociate large recombination intermediates, via branch migration of Holliday junctions through 2.6 kb of DNA. Our data suggest a direct role for FANCM in DNA processing, consistent with the current view that FA proteins coordinate DNA repair at stalled replication forks.

The migration towards Digital Terrestrial Television: challenges for public policy and public broadcasters

This paper initially identifies the main transformations of the television system that are caused by digitalization. Its development in several broadcasting platforms is analyzed as well as the particular obstacles and requirements that are detected for each of them. Due to its technical characteristics and its historical link to the public services, the terrestrial network requires migration strategies different from those strictly commercial, and public intervention might be needed. The paper focuses on such migration strategies towards DTT and identifies the main issues for public intervention in the areas of the digital scenario: technology, business and market transformation and the reception field. Moreover, it describes and classifies the challenges that public broadcasters should confront due to digitalization. This paper finally concludes that the leadership of the public broadcasters during the migration towards DTT is an interesting tool for public policy. The need for foster the digitalization of the terrestrial platform and to achieve certain social and public goal besides the market interest brings an opportunity for public institutions and public broadcasters to work together. That leading role could also be positive for the public service to face its necessary redefinition and reallocation within the digital context.

A qualitative study about immigrant workers’ perceptions of their working conditions in Spain

Background: Spain has recently become an inward migration country. Little is known about the occupational health of immigrant workers. This study aimed to explore the perceptions that immigrant workers in Spain had of their working conditions.Methods: Qualitative, exploratory, descriptive study. Criterion sampling. Data collected between September 2006 and May 2007 through semi-structured focus groups and individual interviews, with a topic guide. One hundred and fifty-eight immigrant workers (90 men/68 women) from Colombia (n = 21), Morocco (n = 39), sub-Saharan Africa (n = 29), Romania (n = 44) and Ecuador (n = 25), who were authorised (documented) or unauthorised (undocumented) residents in five medium to large cities in Spain.Results: Participants described poor working conditions, low pay and health hazards. Perception of hazards appeared to be related to gender and job sector. Informants were highly segregated into jobs by sex, however, so this issue will need further exploration. Undocumented workers described poorer conditions than documented workers, which they attributed to their documentation status. Documented participants also felt vulnerable because of their immigrant status. Informants believed that deficient language skills, non-transferability of their education and training and, most of all, their immigrant status and economic need left them with little choice but to work under poor conditions.Conclusions: The occupational health needs of immigrant workers must be addressed at the job level, while improving the enforcement of existing health and safety regulations. The roles that documentation status and economic need played in these informants' work experiences should be considered and how these may influence health outcomes.

A high prevalence of dual thyroid ectopy in congenital hypothyroidism: evidence for insufficient signaling gradients during embryonic thyroid migration or for the polyclonal nature of the thyroid gland?

BACKGROUND: Thyroid ectopy results from the failure of the thyroid precursor cells to migrate from the primordial pharynx to the anterior part of the neck. Most ectopic thyroids are revealed by congenital hypothyroidism and present as a single round mass at the base of the tongue, with no other thyroid tissue. However, some cases have dual ectopy, with part of the tissue having partially migrated. We hypothesized that this occurs more frequently than previously reported.¦METHODS: To determine the prevalence of dual ectopy, we reviewed the pertechnetate scintigraphies of 81 patients with congenital hypothyroidism from thyroid ectopy diagnosed between 2002 and 2011 at our institution.¦RESULTS: We report a series of seven cases (9%) of dual ectopy, representing an incidence ranging from 1:50,000 to 1:70,000.¦CONCLUSIONS: Almost one in 10 cases with congenital hypothyroidism due to thyroid ectopy has dual ectopy. This suggests that two populations of cells diverged at an early stage of development, which may arise from insufficient signaling gradients in surrounding tissues during early organogenesis or may indirectly support the polyclonal nature of the thyroid.

Peak and persistent excess of genetic diversity following an abrupt migration increase.

Genetic diversity is essential for population survival and adaptation to changing environments. Demographic processes (e.g., bottleneck and expansion) and spatial structure (e.g., migration, number, and size of populations) are known to shape the patterns of the genetic diversity of populations. However, the impact of temporal changes in migration on genetic diversity has seldom been considered, although such events might be the norm. Indeed, during the millions of years of a species' lifetime, repeated isolation and reconnection of populations occur. Geological and climatic events alternately isolate and reconnect habitats. We analytically document the dynamics of genetic diversity after an abrupt change in migration given the mutation rate and the number and sizes of the populations. We demonstrate that during transient dynamics, genetic diversity can reach unexpectedly high values that can be maintained over thousands of generations. We discuss the consequences of such processes for the evolution of species based on standing genetic variation and how they can affect the reconstruction of a population's demographic and evolutionary history from genetic data. Our results also provide guidelines for the use of genetic data for the conservation of natural populations.

Induction of transendothelial migration in normal and malignant human T lymphocytes.

Activated CD 3+ enriched human peripheral blood T cells exhibited potent capacity for transendothelial migration through HUVEC layers in the absence of T cell ***. In contrast, malignant human T cell lines *** no or negligible ability of transendothelial migration in the absence of chemoattractants. Time lapse studies of transendothelial migration of activated CD 3+ enriched peripheral blood T cells through a HUVEC layer showed that the first T cells were detected in the lower compartment of a tissue culture insert after 1 hour and that migration increased to reach a maximum of 25 x 10(4) T cells/hr after 24 hours. Adhesion assays of human T cell lines demonstrated that all T cell lines were capable of adhesion to HUVEC and that adhesion of T cells to HUVECs was primarily mediated by CD11a/CD18 and ICAM-1 interactions. Furthermore, transendothelial migration of CD 3+ enriched human peripheral blood T cells was inhibited by pretreating the T cells with anti-CD 18 monoclonal antibodies. The inability of malignant T cells to migrate through HUVEC layers in the absence of chemoattractants was not due to poor motility per se, since both normal and malignant T cells migrated well on extracellular matrix components as determined by using Boyden chambers. Crosslinking of alpha 1 beta 2 and alpha 4 beta 1 with immobilized monoclonal antibodies induced motile behaviour in activated CD 3 enriched human peripheral blood T cells but not in malignant T cell lines. In conclusion, the differences in the ability of transendothelial migration between normal and malignant human T cells in the absence of chemoattractants is primarily due to the differences in the capacity of alpha 1 beta 2 and alpha 4 beta 1 to trigger motile behaviour in the separate cell types.

Transcriptional activation of the macrophage migration-inhibitory factor gene by the corticotropin-releasing factor is mediated by the cyclic adenosine 3',5'- monophosphate responsive element-binding protein CREB in pituitary cells.

Macrophage migration-inhibitory factor (MIF) has recently been identified as a pituitary hormone that functions as a counterregulatory modulator of glucocorticoid action within the immune system. In the anterior pituitary gland, MIF is expressed in TSH- and ACTH-producing cells, and its secretion is induced by CRF. To investigate MIF function and regulation within pituitary cells, we initiated the characterization of the MIF 5'-regulatory region of the gene. The -1033 to +63 bp of the murine MIF promoter was cloned 5' to a luciferase reporter gene and transiently transfected into freshly isolated rat anterior pituitary cells. This construct drove high basal transcriptional activity that was further enhanced after stimulation with CRF or with an activator of adenylate cyclase. These transcriptional effects were associated with a concomitant rise in ACTH secretion in the transfected cells and by an increase in MIF gene expression as assessed by Northern blot analysis. A cAMP-responsive element (CRE) was identified within the MIF promoter region which, once mutated, abolished the cAMP responsiveness of the gene. Using this newly identified CRE, DNA-binding activity was detected by gel retardation assay in nuclear extracts prepared from isolated anterior pituitary cells and AtT-20 corticotrope tumor cells. Supershift experiments using antibodies against the CRE-binding protein CREB, together with competition assays and the use of recombinant CREB, allowed the detection of CREB-binding activity with the identified MIF CRE. These data demonstrate that CREB is the mediator of the CRF-induced MIF gene transcription in pituitary cells through an identified CRE in the proximal region of the MIF promoter.

Overcoming the ethical dilemmas of skilled migration? An analysis of international narratives on the “brain drain”

Migration-related issues have, since approximately 2000, been the object of increased attention at the international level. This has led, among other things, to the production of international narratives, which aim both at understanding migration and at proposing policy recommendations on how to address it, with the objective of improving the governance of migration at the global level. But this implies overcoming dilemmas stemming from the diverging interests of states and other actors (like NGOs and the private sector). This article examines the way in which international migration narratives address skilled migration, which is characterised by some of the clearest political trade-offs between stakeholders. It argues that these narratives attempt to speak to all parties and conciliate contradictory arguments about what should be done, in order to discursively overcome policy dilemmas and create a consensus. While this is line with the mandate of international organizations, it depoliticises migration issues.

Gendered networks and Mexican migration

In this paper, we investigate how the gendered origin of migrant networks (i.e. matrilineal vs. patrilineal) is associated with aspirations to migrate and subsequent migration behavior. Using longitudinal data from the Mexican Family Life Survey (MxFLS), we follow 3,923 married couples across 139 municipalities over the 2002-2005 period. We find that the networks of both the individual and her/his spouse are associated with aspiring to migrate to the United States. However, one’s own network matters most (i.e. matrilineal networks for women and patrilineal networks for men). On the other hand, in terms of behavior, only matrilineal networks predict a subsequent move to the U.S. for men and women/couples, who are assessed jointly. These findings suggest that our understanding of the role of migrant networks in perpetuating male-centered, labor migration does not necessarily translate once a union has formed. We make the case that future work would do well to account for not only the presence and composition of networks, but also their origin, which in certain circumstances may be the most relevant factor.

Temporary and circular labour migration : reassessing established public policies

Today, Temporary Labour Migration is a fundamental course of action promoted by relevant economic and political agents, such as EC, the GCIM, or the OECD. Based on a specific empirical case study of Temporary and Circular Labour Migration in the Catalonian agrarian sector, which has been distinguished as a particularly successful formula, we identify a new area of interest: the emergence of a new empirical migrant category, the Circular Labour Migrant, which remains theoretically unnamed and lacks public recognition. We argue that, until now, there have been two historical phases regarding temporary labour migration: one of total deregulation and another of partial regulation, led by private actors with support from public institutions, and featuring circularity. IN a developed Welfare State context, it would be normatively pertinent to except a step towards a third phase, one involving the institutionalization of this new mobility category through the elaboration of a public policy.